Anne K. Kenworthy, Ph.D.

Professor

anne.kenworthy@vanderbilt.edu
Faculty Appointments
Professor of Molecular Physiology and Biophysics Associate Professor of Cell and Developmental BiologyAssociate Professor of Cell and Developmental Biology
Education
Ph.D., Cell Biology, Duke University, Durham, North CarolinaB.A., Biology, Kenyon College, Gambier, Ohio
Office Address
718 Light Hall
TN 0615
Research Description
One of the major goals of my research program is to understand the role of membrane microdomains such as lipid rafts and caveolae in health and disease. We address this question using a combination of live cell imaging, cell biology, biophysics, and biochemical approaches. Current projects ongoing in the lab include:

1. How do proteins and lipid cooperate to build functional raft domains?

2. How do bacterial toxins exploit lipid rafts as a mechanism to enter host cells?

3. How do cholesterol and lipid rafts contribute to the progression of Alzheimer's disease?

4. How do mutations in caveolin-1 and defects in caveolae cause human diseases such as breast cancer and pulmonary arterial hypertension?

We are also interested in diffusion, a fundamental process that underlies all cellular functions. We are working in collaboration with biomathematicians to develop widely accessible methods to calibrate, measure and quantify protein and lipid diffusion in living cells. We are also applying these approaches to study novel protein complexes in the autophagy pathway, a housekeeping mechanism used by cells to maintain homeostasis in times of starvation and stress.
Research Keywords
membrane domains, lipid rafts, caveolae, endocytosis, advanced microscopy, FRAP, mathematical modeling, autophagy, Alzheimer's disease, host-pathogen interactions, pulmonary arterial hypertension
Publications
Day CA, Baetz NW, Copeland CA, Kraft LJ, Han B, Tiwari A, Drake KR, De Luca H, Chinnapen DJ, Davidson MW, Holmes RK, Jobling MG, Schroer TA, Lencer WI, Kenworthy AK. Microtubule motors power plasma membrane tubulation in clathrin-independent endocytosis. Traffic [print-electronic]. 2015 Jun; 16(6): 572-90. PMID: 25690058, PMCID: PMC4440230, DOI: 10.1111/tra.12269, ISSN: 1600-0854.

Han B, Tiwari A, Kenworthy AK. Tagging strategies strongly affect the fate of overexpressed caveolin-1. Traffic. 2015 Apr; 16(4): 417-38. PMID: 25639341, PMCID: PMC4440517, DOI: 10.1111/tra.12254, ISSN: 1600-0854.

Renard HF, Simunovic M, Lemière J, Boucrot E, Garcia-Castillo MD, Arumugam S, Chambon V, Lamaze C, Wunder C, Kenworthy AK, Schmidt AA, McMahon HT, Sykes C, Bassereau P, Johannes L. Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis. Nature [print-electronic]. 2015 Jan 1/22/2015; 517(7535): 493-6. PMID: 25517096, PMCID: PMC4342003, PII: nature14064, DOI: 10.1038/nature14064, ISSN: 1476-4687.

Prewitt AR, Ghose S, Frump AL, Datta A, Austin ED, Kenworthy AK, de Caestecker MP. Heterozygous null bone morphogenetic protein receptor type 2 mutations promote SRC kinase-dependent caveolar trafficking defects and endothelial dysfunction in pulmonary arterial hypertension. J. Biol. Chem [print-electronic]. 2015 Jan 1/9/2015; 290(2): 960-71. PMID: 25411245, PMCID: PMC4294523, PII: M114.591057, DOI: 10.1074/jbc.M114.591057, ISSN: 1083-351X.

Day CA, Kenworthy AK. Functions of cholera toxin B-subunit as a raft cross-linker. Essays Biochem. 2015; 57: 135-45. PMID: 25658350, PMCID: PMC4346142, PII: bse0570135, DOI: 10.1042/bse0570135, ISSN: 1744-1358.

Kraft LJ, Nguyen TA, Vogel SS, Kenworthy AK. Size, stoichiometry, and organization of soluble LC3-associated complexes. Autophagy [print-electronic]. 2014 May; 10(5): 861-77. PMID: 24646892, PII: 28175, DOI: 10.4161/auto.28175, ISSN: 1554-8635.

Mazerik JN, Kraft LJ, Kenworthy AK, Tyska MJ. Motor and tail homology 1 (Th1) domains antagonistically control myosin-1 dynamics. Biophys. J. 2014 Feb 2/4/2014; 106(3): 649-58. PMID: 24507605, PMCID: PMC3944834, PII: S0006-3495(14)00012-5, DOI: 10.1016/j.bpj.2013.12.038, ISSN: 1542-0086.

Song Y, Kenworthy AK, Sanders CR. Cholesterol as a co-solvent and a ligand for membrane proteins. Protein Sci [print-electronic]. 2014 Jan; 23(1): 1-22. PMID: 24155031, PMCID: PMC3892294, DOI: 10.1002/pro.2385, ISSN: 1469-896X.

Hanson CA, Drake KR, Baird MA, Han B, Kraft LJ, Davidson MW, Kenworthy AK. Overexpression of caveolin-1 is sufficient to phenocopy the behavior of a disease-associated mutant. Traffic [print-electronic]. 2013 Jun; 14(6): 663-77. PMID: 23469926, PMCID: PMC3674505, DOI: 10.1111/tra.12066, ISSN: 1600-0854.

Kang M, Day CA, Kenworthy AK, DiBenedetto E. Simplified equation to extract diffusion coefficients from confocal FRAP data. Traffic [print-electronic]. 2012 Dec; 13(12): 1589-600. PMID: 22984916, PMCID: PMC3731631, DOI: 10.1111/tra.12008, ISSN: 1600-0854.

Day CA, Kraft LJ, Kang M, Kenworthy AK. Analysis of protein and lipid dynamics using confocal fluorescence recovery after photobleaching (FRAP). Curr Protoc Cytom. 2012 Oct; Chapter 2: Unit2.19. PMID: 23042527, PMCID: PMC3538152, DOI: 10.1002/0471142956.cy0219s62, ISSN: 1934-9300.

Chinnapen DJ, Hsieh WT, te Welscher YM, Saslowsky DE, Kaoutzani L, Brandsma E, D'Auria L, Park H, Wagner JS, Drake KR, Kang M, Benjamin T, Ullman MD, Costello CE, Kenworthy AK, Baumgart T, Massol RH, Lencer WI. Lipid sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1. Dev. Cell. 2012 Sep 9/11/2012; 23(3): 573-86. PMID: 22975326, PMCID: PMC3443397, PII: S1534-5807(12)00366-8, DOI: 10.1016/j.devcel.2012.08.002, ISSN: 1878-1551.

Lapierre LA, Ducharme NA, Drake KR, Goldenring JR, Kenworthy AK. Coordinated regulation of caveolin-1 and Rab11a in apical recycling compartments of polarized epithelial cells. Exp. Cell Res [print-electronic]. 2012 Jan 1/15/2012; 318(2): 103-13. PMID: 22036648, PMCID: PMC3230713, PII: S0014-4827(11)00407-1, DOI: 10.1016/j.yexcr.2011.10.010, ISSN: 1090-2422.

Day CA, Kenworthy AK. Mechanisms underlying the confined diffusion of cholera toxin B-subunit in intact cell membranes. PLoS ONE [print-electronic]. 2012; 7(4): e34923. PMID: 22511973, PMCID: PMC3325267, PII: PONE-D-11-20978, DOI: 10.1371/journal.pone.0034923, ISSN: 1932-6203.

Kraft LJ, Kenworthy AK. Imaging protein complex formation in the autophagy pathway: analysis of the interaction of LC3 and Atg4B(C74A) in live cells using Fo¨rster resonance energy transfer and fluorescence recovery after photobleaching. J Biomed Opt. 2012 Jan; 17(1): 11008. PMID: 22352642, PMCID: PMC3380812, DOI: 10.1117/1.JBO.17.1.011008, ISSN: 1560-2281.

Kang M, DiBenedetto E, Kenworthy AK. Proposed correction to Feder's anomalous diffusion FRAP equations [letter]. Biophys. J. 2011 Feb 2/2/2011; 100(3): 791-2; author reply 793. PMID: 21281595, PMCID: PMC3030171, PII: S0006-3495(10)05261-6, DOI: 10.1016/j.bpj.2010.11.091, ISSN: 1542-0086.

Kang M, Day CA, DiBenedetto E, Kenworthy AK. A quantitative approach to analyze binding diffusion kinetics by confocal FRAP. Biophys. J. 2010 Nov 11/3/2010; 99(9): 2737-47. PMID: 21044570, PMCID: PMC2965996, PII: S0006-3495(10)01114-8, DOI: 10.1016/j.bpj.2010.09.013, ISSN: 1542-0086.

Cha B, Zhu XC, Chen W, Jones M, Ryoo S, Zachos NC, Chen TE, Lin R, Sarker R, Kenworthy AK, Tse M, Kovbasnjuk O, Donowitz M. NHE3 mobility in brush borders increases upon NHERF2-dependent stimulation by lyophosphatidic acid. J. Cell. Sci [print-electronic]. 2010 Jul 7/15/2010; 123(Pt 14): 2434-43. PMID: 20571054, PMCID: PMC2936692, PII: jcs.056713, DOI: 10.1242/jcs.056713, ISSN: 1477-9137.

Drake KR, Kang M, Kenworthy AK. Nucleocytoplasmic distribution and dynamics of the autophagosome marker EGFP-LC3. PLoS ONE. 2010; 5(3): e9806. PMID: 20352102, PMCID: PMC2843706, DOI: 10.1371/journal.pone.0009806, ISSN: 1932-6203.

Kang M, Day CA, Drake K, Kenworthy AK, DiBenedetto E. A generalization of theory for two-dimensional fluorescence recovery after photobleaching applicable to confocal laser scanning microscopes. Biophys. J. 2009 Sep 9/2/2009; 97(5): 1501-11. PMID: 19720039, PMCID: PMC2749741, PII: S0006-3495(09)01122-9, DOI: 10.1016/j.bpj.2009.06.017, ISSN: 1542-0086.

Korade Z, Kenworthy AK, Mirnics K. Molecular consequences of altered neuronal cholesterol biosynthesis. J. Neurosci. Res. 2009 Mar; 87(4): 866-75. PMID: 18951487, PMCID: PMC4360921, DOI: 10.1002/jnr.21917, ISSN: 1097-4547.

Day CA, Kenworthy AK. Tracking microdomain dynamics in cell membranes. Biochim. Biophys. Acta [print-electronic]. 2009 Jan; 1788(1): 245-53. PMID: 19041847, PMCID: PMC2792115, PII: S0005-2736(08)00353-2, DOI: 10.1016/j.bbamem.2008.10.024, ISSN: 0006-3002.

Kiskowski MA, Hancock JF, Kenworthy AK. On the use of Ripley's K-function and its derivatives to analyze domain size. Biophys J. 2009; 97: 1095-103.

Korade Z, Kenworthy AK. Lipid rafts, cholesterol, and the brain. Neuropharmacology [print-electronic]. 2008 Dec; 55(8): 1265-73. PMID: 18402986, PMCID: PMC2638588, PII: S0028-3908(08)00064-6, DOI: 10.1016/j.neuropharm.2008.02.019, ISSN: 0028-3908.

Kang M, Kenworthy AK. A closed-form analytic expression for FRAP formula for the binding diffusion model [letter]. Biophys. J [print-electronic]. 2008 Jul; 95(2): L13-5. PMID: 18487305, PMCID: PMC2440465, PII: S0006-3495(08)70221-2, DOI: 10.1529/biophysj.108.135913, ISSN: 1542-0086.

Kenworthy AK. Have we become overly reliant on lipid rafts? Talking Point on the involvement of lipid rafts in T-cell activation. EMBO Rep. 2008 Jun; 9(6): 531-5. PMID: 18516088, PMCID: PMC2427377, PII: embor200892, DOI: 10.1038/embor.2008.92, ISSN: 1469-3178.

Wolf AA, Jobling MG, Saslowsky DE, Kern E, Drake KR, Kenworthy AK, Holmes RK, Lencer WI. Attenuated endocytosis and toxicity of a mutant cholera toxin with decreased ability to cluster ganglioside GM1 molecules. Infect. Immun [print-electronic]. 2008 Apr; 76(4): 1476-84. PMID: 18212085, PMCID: PMC2292862, PII: IAI.01286-07, DOI: 10.1128/IAI.01286-07, ISSN: 1098-5522.

Kenworthy AK. Breaking up isn't so hard to do. Biophys. J [print-electronic]. 2007 Nov 11/1/2007; 93(9): 2984-5. PMID: 17660323, PMCID: PMC2025653, PII: S0006-3495(07)71552-7, DOI: 10.1529/biophysj.107.115618, ISSN: 0006-3495.

Roland JT, Kenworthy AK, Peranen J, Caplan S, Goldenring JR. Myosin Vb interacts with Rab8a on a tubular network containing EHD1 and EHD3. Mol. Biol. Cell [print-electronic]. 2007 Aug; 18(8): 2828-37. PMID: 17507647, PMCID: PMC1949367, PII: E07-02-0169, DOI: 10.1091/mbc.E07-02-0169, ISSN: 1059-1524.

Kiskowski MA, Kenworthy AK. In silico characterization of resonance energy transfer for disk-shaped membrane domains. Biophys. J [print-electronic]. 2007 May 5/1/2007; 92(9): 3040-51. PMID: 17325021, PMCID: PMC1852346, PII: S0006-3495(07)71113-X, DOI: 10.1529/biophysj.106.093245, ISSN: 0006-3495.

Kenworthy AK. Fluorescence recovery after photobleaching studies of lipid rafts. Methods Mol. Biol. 2007; 398: 179-92. PMID: 18214381, DOI: 10.1007/978-1-59745-513-8_13, ISSN: 1064-3745.

Kenworthy AK. Fluorescence-based methods to image palmitoylated proteins. Methods. 2006 Oct; 40(2): 198-205. PMID: 17012033, PII: S1046-2023(06)00168-X, DOI: 10.1016/j.ymeth.2006.06.021, ISSN: 1046-2023.

Hinow P, Rogers CE, Barbieri CE, Pietenpol JA, Kenworthy AK, DiBenedetto E. The DNA binding activity of p53 displays reaction-diffusion kinetics. Biophys. J [print-electronic]. 2006 Jul 7/1/2006; 91(1): 330-42. PMID: 16603489, PMCID: PMC1479054, PII: S0006-3495(06)71732-5, DOI: 10.1529/biophysj.105.078303, ISSN: 0006-3495.

Bush WS, Ihrke G, Robinson JM, Kenworthy AK. Antibody-specific detection of caveolin-1 in subapical compartments of MDCK cells. Histochem. Cell Biol [print-electronic]. 2006 Jul; 126(1): 27-34. PMID: 16770576, DOI: 10.1007/s00418-006-0144-y, ISSN: 0948-6143.

Goodwin JS, Kenworthy AK. Photobleaching approaches to investigate diffusional mobility and trafficking of Ras in living cells. Methods. 2005 Oct; 37(2): 154-64. PMID: 16288889, PII: S1046-2023(05)00130-1, DOI: 10.1016/j.ymeth.2005.05.013, ISSN: 1046-2023.

Kenworthy AK. Fleeting glimpses of lipid rafts: how biophysics is being used to track them. J. Investig. Med. 2005 Sep; 53(6): 312-7. PMID: 16207468, ISSN: 1081-5589.

Goodwin JS, Drake KR, Remmert CL, Kenworthy AK. Ras diffusion is sensitive to plasma membrane viscosity. Biophys. J [print-electronic]. 2005 Aug; 89(2): 1398-410. PMID: 15923235, PMCID: PMC1366624, PII: biophysj.104.055640, DOI: 10.1529/biophysj.104.055640, ISSN: 0006-3495.

Goodwin JS, Drake KR, Rogers C, Wright L, Lippincott-Schwartz J, Philips MR, Kenworthy AK. Depalmitoylated Ras traffics to and from the Golgi complex via a nonvesicular pathway. J. Cell Biol. 2005 Jul 7/18/2005; 170(2): 261-72. PMID: 16027222, PMCID: PMC2171405, PII: jcb.200502063, DOI: 10.1083/jcb.200502063, ISSN: 0021-9525.

Hess, S.T., Kumar, M., Verma, A., Farrington, J., Kenworthy, A., and Zimmerberg, J.. Quantitative electron microscopy and fluorescence spectroscopy of the membrane distribution of influenza hemagglutinin. J. Cell Biol. 2005; 169: 965-76.

Kenworthy AK, Nichols BJ, Remmert CL, Hendrix GM, Kumar M, Zimmerberg J, Lippincott-Schwartz J. Dynamics of putative raft-associated proteins at the cell surface. J. Cell Biol [print-electronic]. 2004 Jun 6/7/2004; 165(5): 735-46. PMID: 15173190, PMCID: PMC2172371, PII: jcb.200312170, DOI: 10.1083/jcb.200312170, ISSN: 0021-9525.

Kenworthy A. Peering inside lipid rafts and caveolae. Trends Biochem. Sci. 2002 Sep; 27(9): 435-7. PMID: 12217512, PII: S0968-0004(02)02178-3, ISSN: 0968-0004.

Available Postdoctoral Position Details
Posted: 8/12/2013
Postdoctoral positions are currently available for highly motivated individuals to carry out research in two areas:

1. Postdoctoral position currently available to study the role of bacterial toxins in stabilizing and manipulating membrane rafts and mechanisms responsible for toxin entry into host cells via clathrin-independent endocytosis. Experience with live cell imaging, membrane trafficking, and/or model membrane systems is a plus.

2. Postdoctoral position available to develop methods to measure kinetic rate constants in single cells using quantitative fluorescence microscopy and apply these methods to study protein complex formation and reaction-diffusion events at the cellular level. Experience in mathematical modeling and/or FRAP, FCS, and photoactivation approaches is a plus.

To apply, please email your CV and the contact information for 3 references to anne.kenworthy@vanderbilt.edu.